Dataset Information

Effects of Manganese on Genomic Integrity in the Multicellular Model Organism Caenorhabditis elegans.

ABSTRACT: Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism Caenorhabditis elegans to investigate the mode of action of Mn toxicity, focusing on genomic integrity by means of DNA damage and DNA damage response. Experiments were conducted to analyze Mn bioavailability, lethality, and induction of DNA damage. Different deletion mutant strains were then used to investigate the role of base excision repair (BER) and dePARylation (DNA damage response) proteins in Mn-induced toxicity. The results indicate a dose- and time-dependent uptake of Mn, resulting in increased lethality. Excessive exposure to Mn decreases genomic integrity and activates BER. Altogether, this study characterizes the consequences of Mn exposure on genomic integrity and therefore broadens the molecular understanding of pathways underlying Mn-induced toxicity. Additionally, studying the basal poly(ADP-ribosylation) (PARylation) of worms lacking poly(ADP-ribose) glycohydrolase (PARG) parg-1 or parg-2 (two orthologue of PARG), indicates that parg-1 accounts for most of the glycohydrolase activity in worms.

SUBMITTER: Nicolai MM

PROVIDER: S-EPMC8535284 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i>.

Nicolai Merle M MM Weishaupt Ann-Kathrin AK Baesler Jessica J Brinkmann Vanessa V Wellenberg Anna A Winkelbeiner Nicola N Gremme Anna A Aschner Michael M Fritz Gerhard G Schwerdtle Tanja T Bornhorst Julia J

International journal of molecular sciences 20211009 20

Although manganese (Mn) is an essential trace element, overexposure is associated with Mn-induced toxicity and neurological dysfunction. Even though Mn-induced oxidative stress is discussed extensively, neither the underlying mechanisms of the potential consequences of Mn-induced oxidative stress on DNA damage and DNA repair, nor the possibly resulting toxicity are characterized yet. In this study, we use the model organism <i>Caenorhabditis elegans</i> to investigate the mode of action of Mn to ...[more]

PMID: 34681565

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Project description:Grapes and their products are known to have been used for the treatment of diseases throughout history.It was aimed to investigate the effects of Erzincan Cimin grapes on an organism model of Caenorhabditis elegans N2 wild type and C. elegans BS913 strains with gonad cancer.The effects of methanol extracts of the skin and seeds of Erzincan Cimin grapes were examined separately on C. elegans N2 wild type and an effect was determined on lifespan. By applying GS-MS analysis, a potential agent substance was determined in the skin and seed methanol extracts. This substance was purchased and the effects of this substance were investigated on lifespan and fertility in C. elegans BS913 strains with gonad cancer. In addition, the effects on young subjects exposed to this agent substance in L1 form were investigated.Grape seed and skin methanol extract was observed to prolong the lifespan most at a dose of 10 mg/100 mL. Lifespan was determined to be at a maximum in a gonad cancer organism model with benzothiazol at a dose of 50 ppm. At the same dose, positive effects were determined on the fertility of strains with cancer. When the effects of benzothiazol were examined on young L1 forms, an evident retardation of growth was determined at doses of 10, 50, and 100 ppm.Owing to anti-carcinogenic effects of benzothiazol and benzothiazol-derived substances, they can be considered as agent substances in academic studies related to cancer.The effects of methanol extracts of the skin and seeds of Erzincan Cimin grapes were examined on C. elegans N2 wild type and an effect was determined on lifespanThrough GS-MS analysis, benzothiazol was determined in the skin methanol extractsBenzothiazol was purchased and the effects of this substance were investigated on lifespan and fertility in C. elegans BS913 strains with gonad cancerThe effects on young subjects exposed to benzothiazol in L1 formGrape seed, skin methanol extract, and benzothiazol was observed to prolong the lifespanPositive effects were determined on the fertility of gonad cancer strains. Abbreviations used: GC-MS: gas chromatography and mass spectrometry; C. elegans: Caenorhabditis elegans; NGM: Nematode growth medium; E. coli: Escherichia coli; FUDR: Fluorodeoxyuridine; LDL: Low-density lipoprotein.

Dataset Information

Effects of Manganese on Genomic Integrity in the Multicellular Model Organism Caenorhabditis elegans.

Publications

Effects of Manganese on Genomic Integrity in the Multicellular Model Organism <i>Caenorhabditis elegans</i>.

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